14IN - How to Optimise Endocrine Therapy

Abstract

For post-menopausal women with early stage ER+ breast cancer, aromatase inhibitors are recommended to be part of adjuvant endocrine therapy either as up-front therapy or as a switch strategy following initial tamoxifen therapy. Both approaches are equally effective, and both are superior to tamoxifen alone for 5 years. The current duration for aromatase inhibitors given as adjuvant therapy is 5 years based on current safety and efficacy data. However, the optimal duration of adjuvant endocrine therapy is currently unknown, and extended adjuvant therapy with aromatase inhibitors after tamoxifen is an increasingly utilised strategy for reducing ongoing risk of recurrence, especially for those deemed to be at greater risk such as those with node-positive disease or other indicators for late relapse. In pre-menopausal women with ER+ early breast cancer the added benefit of ovarian suppression over and above tamoxifen remains unknown. In women aged <40 years, added benefit may exist, but must be weighed up against both short and long-term tolerability. For all patients, evolving data suggest that molecular profiling of ER+ breast cancer using assays such as Oncotype Dx or PAM50 can identify those subtypes at low risk of recurrence for whom the addition of adjuvant chemotherapy over and above endocrine therapy is not indicated. To date biomarkers, although clearly of prognostic value, have not been shown to identify those more likely to benefit preferentially from aromatase inhibitors rather than tamoxifen. Thus clinical criteria remain the most important in making decisions about choice of agents, including an assessment of toxicities that may occur with either approaches. Novel strategies for adjuvant endocrine therapy are being explored in ongoing clinical trials, including the integration of signalling therapies in combination with aromatase inhibitors based on the recent success of BOLERO-2 in the advanced disease setting. S.R.D. Johnston: Research funding from AstraZeneca